Curated from Technology Networks

Research has long hinted that the ketogenic diet may help manage autoimmune diseases like multiple sclerosis (MS) by dampening overactive immune responses. A new study from the University of California, San Francisco (UCSF) has offered promising evidence to support this theory. Scientists found that, in a mouse model of MS, the keto diet induced the production of specific compounds in the gut, which helped to reduce MS symptoms. If these findings hold true in humans, the research could open the door to new treatment approaches for autoimmune disorders using diet-based supplements rather than strict dietary restrictions.

The ketogenic diet and immune modulation

The ketogenic (keto) diet involves severely limiting carbohydrate intake while increasing fat consumption, causing the body to shift from burning carbohydrates for energy to breaking down fat. This shift results in the production of ketone bodies, which serve as an alternative fuel source and have been shown to influence immune function. The UCSF team’s findings, published in Cell Reports, provide insight into how this dietary shift impacts immune-related inflammation.

Key findings: ketones, bacteria, and immune regulation

The study showed that a ketone body known as β-hydroxybutyrate (βHB) played a central role in reducing inflammation in mice. In the study, mice on a keto diet produced higher levels of βHB, which in turn affected the activity of gut bacteria. Specifically, the gut bacterium Lactobacillus murinus responded to βHB by producing a compound called indole lactic acid (ILA), which blocked the activation of T helper 17 (Th17) cells. These Th17 cells are commonly involved in MS and other autoimmune diseases, where they drive immune-related inflammation.

Experimental results: supplementing βHB and isolating bacteria

To understand the gut’s role in this process, the researchers first examined mice unable to naturally produce βHB in their intestines. These mice exhibited more severe inflammatory symptoms compared to those that could produce the compound. However, supplementing the diets of these βHB-deficient mice with additional βHB reduced their inflammation levels, showing that βHB’s presence is critical in managing immune responses in the gut.

The team further investigated by isolating bacterial strains from the intestines of mice on different diets (keto, high-fat, and βHB-supplemented high-fat diets). They found that mice on the βHB-supplemented diets had higher levels of L. murinus, which produced ILA – a metabolite shown to interact with the immune system and reduce inflammation. Genome sequencing and mass spectrometry confirmed that L. murinus specifically was responsible for producing ILA.

Testing potential treatments with ILA and L. murinus

The team explored whether treating the MS mice with either ILA or L. murinus would directly affect disease severity. Results indicated that both treatments helped reduce MS symptoms in the mice, suggesting that specific bacterial compounds might offer a therapeutic benefit. However, as lead researcher Peter Turnbaugh, PhD, cautions, these effects still need testing in humans to confirm their efficacy and safety.

Future directions and implications for treatment

This study’s findings highlight the potential of using keto-related supplements to mimic some benefits of the diet without requiring strict adherence to dietary restrictions. For patients with autoimmune disorders, a supplement-based approach might offer a more accessible and tolerable option. Turnbaugh emphasized that while the results are promising, further research is necessary to understand how this approach might apply in clinical settings.

“The big question now is how much of this will translate into actual patients. But I think these results provide hope for the development of a more tolerable alternative to helping those people than asking them stick to a challenging and restrictive diet.”

Dr. Peter Turnbaugh

With additional testing in humans, this research could lead to new options for people with autoimmune diseases, allowing them to gain the immune-modulating effects of a keto diet without the need for strict dietary limitations.

Reference: Alexander M, Upadhyay V, Rock R, et al. A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity. Cell Reports. 2024:114891. doi: 10.1016/j.celrep.2024.114891

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